The effects of concurrent atorvastatin therapy on the pharmacokinetics of intravenous midazolam.

Hdl Handle:
http://hdl.handle.net/10147/208990
Title:
The effects of concurrent atorvastatin therapy on the pharmacokinetics of intravenous midazolam.
Authors:
Mc Donnell, C G; Harte, S; O'Driscoll, J; O'Loughlin, C; Van Pelt, F N A M; Shorten, G D
Affiliation:
Department of Anaesthesia, Cork University Hospital, Ireland., conormcdonnell@hotmail.com
Citation:
Anaesthesia. 2003 Sep;58(9):899-904.
Journal:
Anaesthesia
Issue Date:
3-Feb-2012
URI:
http://hdl.handle.net/10147/208990
PubMed ID:
12911366
Abstract:
Midazolam is a commonly used anaesthetic agent and is metabolised by the 3A4 isoform of the cytochrome P450 enzyme system. Atorvastatin is also metabolised by cytochrome P450 3A4 and, in vitro, atorvastatin inhibits the cytochrome P450 3A4-mediated metabolism of mexazolam. We hypothesised that concurrent administration of atorvastatin and midazolam would result in altered midazolam pharmacokinetics. Fourteen patients scheduled to undergo general anaesthesia for elective surgery were recruited in a matched pair design to receive intravenous midazolam (0.15 mg.kg-1). Of these patients, seven were taking long-term atorvastatin. Atorvastatin patients demonstrated a greater area under the curve (889.4 (standard deviation 388.6) ng-h.ml-1) vs. control patients (629.1 (standard deviation 197.2) ng-h.ml-1) (p < 0.05). Patients taking atorvastatin also demonstrated a decreased clearance (0.18 (standard deviation 0.08) l-kg. h-1) vs. control patients (0.27 (standard deviation 0.08) l-kg.h-1) (p < 0.05). This study suggests that chronically administered atorvastatin decreases the clearance of intravenously administered midazolam.
Language:
eng
MeSH:
Aged; Anesthesia, General; Anesthetics, Intravenous/*blood; Anticholesteremic Agents/*pharmacology; Drug Interactions; Female; Half-Life; Heptanoic Acids/*pharmacology; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology; Male; Matched-Pair Analysis; Midazolam/*blood; Middle Aged; Pyrroles/*pharmacology
ISSN:
0003-2409 (Print); 0003-2409 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorMc Donnell, C Gen_GB
dc.contributor.authorHarte, Sen_GB
dc.contributor.authorO'Driscoll, Jen_GB
dc.contributor.authorO'Loughlin, Cen_GB
dc.contributor.authorVan Pelt, F N A Men_GB
dc.contributor.authorShorten, G Den_GB
dc.date.accessioned2012-02-03T15:09:19Z-
dc.date.available2012-02-03T15:09:19Z-
dc.date.issued2012-02-03T15:09:19Z-
dc.identifier.citationAnaesthesia. 2003 Sep;58(9):899-904.en_GB
dc.identifier.issn0003-2409 (Print)en_GB
dc.identifier.issn0003-2409 (Linking)en_GB
dc.identifier.pmid12911366en_GB
dc.identifier.urihttp://hdl.handle.net/10147/208990-
dc.description.abstractMidazolam is a commonly used anaesthetic agent and is metabolised by the 3A4 isoform of the cytochrome P450 enzyme system. Atorvastatin is also metabolised by cytochrome P450 3A4 and, in vitro, atorvastatin inhibits the cytochrome P450 3A4-mediated metabolism of mexazolam. We hypothesised that concurrent administration of atorvastatin and midazolam would result in altered midazolam pharmacokinetics. Fourteen patients scheduled to undergo general anaesthesia for elective surgery were recruited in a matched pair design to receive intravenous midazolam (0.15 mg.kg-1). Of these patients, seven were taking long-term atorvastatin. Atorvastatin patients demonstrated a greater area under the curve (889.4 (standard deviation 388.6) ng-h.ml-1) vs. control patients (629.1 (standard deviation 197.2) ng-h.ml-1) (p < 0.05). Patients taking atorvastatin also demonstrated a decreased clearance (0.18 (standard deviation 0.08) l-kg. h-1) vs. control patients (0.27 (standard deviation 0.08) l-kg.h-1) (p < 0.05). This study suggests that chronically administered atorvastatin decreases the clearance of intravenously administered midazolam.en_GB
dc.language.isoengen_GB
dc.subject.meshAgeden_GB
dc.subject.meshAnesthesia, Generalen_GB
dc.subject.meshAnesthetics, Intravenous/*blooden_GB
dc.subject.meshAnticholesteremic Agents/*pharmacologyen_GB
dc.subject.meshDrug Interactionsen_GB
dc.subject.meshFemaleen_GB
dc.subject.meshHalf-Lifeen_GB
dc.subject.meshHeptanoic Acids/*pharmacologyen_GB
dc.subject.meshHumansen_GB
dc.subject.meshHydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacologyen_GB
dc.subject.meshMaleen_GB
dc.subject.meshMatched-Pair Analysisen_GB
dc.subject.meshMidazolam/*blooden_GB
dc.subject.meshMiddle Ageden_GB
dc.subject.meshPyrroles/*pharmacologyen_GB
dc.titleThe effects of concurrent atorvastatin therapy on the pharmacokinetics of intravenous midazolam.en_GB
dc.contributor.departmentDepartment of Anaesthesia, Cork University Hospital, Ireland., conormcdonnell@hotmail.comen_GB
dc.identifier.journalAnaesthesiaen_GB
dc.description.provinceMunster-
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